替比夫定联合双环醇治疗HBeAg阳性慢性乙型肝炎患者的疗效分析

目的研究替比夫定联合双环醇片治疗HBeAg阳性慢性乙型肝炎(CHB)患者的疗效和安全性。方法选择133例未应用其他抗病毒药物的HBeAg阳性CHB患者,随机分两组接受治疗。试验组67例,每日口服替比夫定600 mg,同时每日服用双环醇片75 mg;对照组66例,仅给予每日口服替比夫定600 mg,两组均连续用药104周。观察治疗前后血清ALT水平及病毒学指标方面的改变。结果两组血清均明显下降,试验组更为显著(P<0.01)。治疗12周时,两组患者在HBeAg转阴率及血清学转换方面比较,差异均无统计学意义,随治疗时间延长,在治疗24、52、104周各时间点,实验组HBeAg转阴率及血清学转换均高于对照组,差异均有统计学意义。两组HBV DNA水平均出现明显下降,但各治疗时间点HBV DNA下降水平及检测不到比率比较,差异无统计学意义(P>0.05)。治疗52周时,治疗组和对照组各出现2例和3例耐药,耐药率分别为4.69%和7.81%,两组比较,差异无统计学意义(P>0.05),治疗104周时,治疗组耐药5例,对照组耐药13例,耐药率分别为7.81%和20.31%,两组比较,差异有统计学意义(P<0.05)。2组均未发生与研究药物相关的不良反应。结论替比夫定与双环醇片联合应用治疗HBeAg阳性CHB在肝功能及病毒学方面取得较好疗效且安全。     

慢性乙型肝炎抗病毒治疗重在规范:口服核苷(酸)类似物类药物的临床应用原则

口服核苷(酸)类似物应用于慢性乙型肝炎的抗病毒治疗已近10年.从1998年拉米夫定到2003年阿德福韦酯,再到2006年恩替卡韦和2007年替比夫定,乃至不久后的替诺福韦、克拉夫定、恩曲他滨等药物的引入和广泛应用业已证明,口服核苷(酸)类药物已使慢性乙型肝炎抗病毒治疗获得巨大进展.口服核苷(酸)类似物在慢性乙型肝炎抗病毒治疗中的"有效性"、"可行性"、"安全性"已获得临床的广泛认同,其耐药性的产生也引起高度重视.单一或联合核苷(酸)类似物的使用,可使临床上90%以上的患者达到持续抑制HBV复制这一慢性乙型肝炎治疗的基本目标.     

慢性乙型肝炎患者认知重评策略与生活满意度关系的调查研究

目的探讨CHB患者认知重评策略与生活满意度的关系。方法采用情绪调节问卷（ERS）、生活满意度量表（SWLS）、心理韧性量表（CD-RISC）对130例CHB患者进行施测。结果 CHB患者的认知重评和生活满意度、心理韧性显著相关（P〈0.05）,认知重评与心理韧性各维度也存在显著相关（P〈0.05）,且CHB患者的心理韧性在认知重评策略和生活满意度上起完全中介作用。结论CHB患者的认知重评策略通过心理韧性影响患者的生活满意度。     

慢性乙型肝炎病毒感染者肝组织HBcAg表达与临床及病理特征的关系

目的探讨慢性HBV感染者肝组织HBcAg表达及其在亚细胞结构的分布与血清HBeAg表达、HBV DNA水平及肝组织病理学损害的关系。方法对371例慢性HBV感染者进行肝穿刺活检,检测肝组织HBcAg、血清HBV标志物、血清ALT及血清中的HBV DNA水平。比较HBcAg阴性与HBcAg表达为核型、浆型、浆核型的病例血清HBeAg阳性率、HBV DNA水平与肝组织病理学损害的关系。同时观察血清HBeAg阳性组及阴性组,肝细胞HBcAg不同表达形式在不同年龄阶段的分布特点。结果肝组织HBcAg阴性组血清HBeAg阳性率为33.1%,比HBcAg阳性各组均低(核型组68.7%;浆型组62.3%;浆核型组84.5%),炎症分级G≥2的患者比例为21.5%,低于HBcAg阳性各组(核型34.3%;浆型67.7%;浆核型69.1%),P<0.01,差异有统计学意义。其中浆型组及浆核型组G≥2的患者比例高于核型组,P<0.01,差异有统计学意义。血清HBV DNA水平在核型组高于其他各组,P<0.05,差异有统计学意义。血清HBeAg阳性组中,年龄≤20岁的HBcAg肝细胞表达为核型的比例为61.5%,高于年龄为20～39岁的11.5%及年龄≥40岁的12.3%,随年龄增加浆型及浆核型表达的比例增加,在三组分别为23.1%/7.7%、26.4%/30.8%、28.4%/45.4%,差异有统计学意义(χ2=53.74,P<0.01)。血清HBeAg阴性组中,肝组织HBcAg阴性的在各年龄组均占大部分(68.1%、61.5%、40.4%)。随年龄增加浆型及浆核型表达的比例增加,在三组分别为4.6%/4.6%、19.3%/7.7%、26.9%/20.4%,差异无统计学意义(χ2=8.94,P>0.05)。结论慢性乙型肝炎患者肝组织HBcAg表达与血清HBeAg表达有关。浆型及浆核型HBcAg表达常伴随明显的肝组织炎症。HBcAg表达形式在不同年龄阶段具有不同特点,与其所处自然史阶段有关。     

提高HBeAg阳性慢性乙型肝炎患者的HBeAg血清学转换率的治疗对策

乙型肝炎病毒e抗原(HBeAg)阳性的慢性乙型肝炎患者自发地或治疗后出现HBeAg血清学转换,伴有血中HBVDNA的下降、丙氨酸转氨酶(ALT)恢复正常、临床病情的缓解、肝脏组织炎症活动度减轻,部分患者在HBeAg血清学转换后可出现乙肝肝炎病毒表面抗原(HBsAg)的血清学转换,是HBeAg阳性慢性乙型肝炎的治疗目标[1].     

慢性乙型肝炎抗病毒治疗的现状和进展

全球有20亿人曾经受到乙型肝炎病毒（HBV）的感染，其中约4亿发展成为慢性乙型肝炎患者，中国约占其中的三分之一（约1．3亿）。慢性乙型肝炎是导致肝硬化、肝癌、肝功能衰竭的主要原因，而肝硬化和原发性肝癌的发生与HBV的持续复制密切相关。因此，抗病毒治疗是慢性乙型肝炎治疗的关键。近年来，越来越多的抗病毒药物应用于临床，其疗效和存在的问题得到逐步深入的认识，故选择何种抗病毒药物成为临床上经常遇到的问题。现将抗病毒药物治疗慢性乙型肝炎的现状和进展综述如下。     

慢性乙型肝炎抗病毒治疗起于探索,重在规范

自2007年起至今,慢性乙型肝炎(CHB)治疗及研究领域"热闹"非凡.由于近年在我国大陆、香港、台湾及欧洲等地对HBV感染自然史的深入了解,认为病毒负荷和肝炎预后有重要关系,而且发现HBeAg阴性CHB病毒负荷及肝功能呈波动性改变,加上抗病毒药物不断更新,病毒检测方法日趋完善,所以原有乙型肝炎治疗指南亟待改进.     

人乙型肝炎免疫球蛋白定量清除新生儿乙型肝炎病毒表面抗原的研究

目的 根据新生儿出生时HBsAg和HBV DNA的载量,调整人乙型肝炎免疫球蛋白使用量,以期更有效地阻断HBV的母婴传播. 方法 收集出生2h内静脉血HBsAg阳性新生儿资料125例.分为研究组64例,对照组61例,研究组根据新生儿出生时HBsAg感染量调整乙型肝炎免疫球蛋白使用量,与对照组比较新生儿12个月龄以上治疗效果.计量资料采用非正态分布采用秩和检验,计数资料采用x2检验.结果 2组新生儿出生时HBsAg和HBV DNA检测值的差异均无统计学意义(p 值均＞0.05).研究组出生HBV感染新生几64例,12月龄以上成功清除HBsAg者53例,成功清除率为82.8％,感染11例(1.2％).对照组出生HBV感染新生儿61例,12月龄以上成功清除HBsAg者35例,成功清除率为57.4％,感染26例(3.1％).2组出生HBV感染新生儿12个月龄以上清除HBsAg效果比较,x2=9.696,P＜0.05,差异有统计学意义.结论 根据新生儿的HBsAg感染量调整使用乙型肝炎免疫球蛋白,可提高乙型肝炎母婴传播的阻断成功率.     

慢性乙型肝炎患者血清HBV DNA、HBeAg与肝组织HBcAg及炎症分级的关系

目的 探讨慢性乙型肝炎（CHB）患者血清HBV DNA、HBeAg与肝组织HBcAg及炎症分级的关系.方法 回顾性分析250例CHB肝穿刺患者,按血清HBV DNA水平,分为A组（＜3 log10 IU/ml）45例,B组（3～6 log10 IU/ml）138例,C组（＞6 log10 IU/ml）67例.按HBeAg阴阳性不同分为阳性组142例,阴性组108例.分别与肝组织中HBcAg水平、肝组织炎症分级进行比较,分析彼此的相关性,率的比较用卡方检验及确切概率法,相关性分析采用直线相关分析.结果 血清HBV DNA不同水平与肝组织HBcAg免疫组化比较差异有统计学意义（χ2=11.1,P=0.05）,两者之间呈正相关（r=0.75,P=0.001）;与肝组织炎症分级（G）比较差异无统计学意义（χ2=13.3,P=0.075）,两者之间也无相关性（r=0.04,P=0.325）.HBeAg阳性和阴性分组与肝组织中HBcAg水平比较差异有统计学意义（χ2=6.64,P=0.01）,两者之间呈正相关（r=0.56,P=0.001）;与肝组织炎症分级（G）比较差异无统计学意义（χ2=8.43,P=0 065）,两者之间也无相关性（r=0.06,P=0.415）.结论 CHB患者肝组织HBcAg表达更能反映出肝内HBV复制状态,患者血清中测不出病毒标志物时,可以考虑肝穿刺以观察肝组织中HBcAg表达来判断HBV复制状态具有重要意义.     

追求持久免疫控制:写在聚乙二醇干扰素α上市10周年

国内外对于慢性乙型肝炎(CHB)抗病毒治疗的目标是清晰一致的,即最大限度地长期抑制病毒复制,从而延缓肝脏疾病的进展,减少肝硬化、肝细胞癌或肝衰竭的发生.但对于治疗过程中的治疗终点仍存在争议.2012年版EASL指南在2009年版的基础上提出的治疗终点仍然包括理想治疗终点、满意治疗终点、基本治疗终点:理想治疗终点是停止治疗后持续HBsAg消失,伴有或不伴抗-HBs血清学转换;满意治疗终点是停止治疗后持续病毒学应答和生物化学应答;基本治疗终点是在长期治疗中维持病毒学应答[1].     

慢性乙型病毒性肝炎的治疗策略及进展

慢性乙型病毒性肝炎(简称“乙肝”)严重威胁着人类的健康。虽然近年来,新的抗病毒药物不断出现,给慢性乙肝的治疗提供了新的手段,也解决了一定的临床问题。但由于乙型肝炎病毒(HBV)本身的难治性以及慢性乙型肝炎临床表现的复杂多样性,使慢性乙型肝炎的治疗前景仍然不容乐观。尤其是近几年来,乙型病毒性肝炎的流行又出现了新变化、新特点,给临床医生提出了新的问题与挑战。中华医学会肝病学分会和中华医学会感染病学分会组织国内有关专家,在参考国内外最新研究成果的基础上,遵照循证医学的原则,在2005年12月份制订了《慢性乙型肝炎防治指南…     

Pegylated interferon for treatment of hepatitis C

GASTROENTEROLOGY 2001;120:4-4     

Treatment of chronic hepatitis C in nonresponders to interferon monotherapy

Sixty percent of patients fail to respond to interferon monotherapy. African-Americans with hepatitis C appear to respond less well to interferon monotherapy. Retreatment with a higher dose of consensus interferon for 48 weeks has led to a sustained virologic response rate of 13%. As a group, interferon nonresponders who breakthrough while on interferon monotherapy seem to have a more favorable response rate to a repeat course of treatment. Retreatment with interferon and ribavirin for 6 months in nonresponders led to a sustained virologic response rate of 21%. Preliminary results from two trials in the United States demonstrate similar treatment efficacy. There is now evidence that maintenance interferon therapy may also be beneficial in interferon monotherapy nonresponders.     

Case selection for interferon treatment of hepatitis C

To establish a case selection algorithm for the treatment of hepatitis C, predictive factors were studied and reported articles were reviewed and analysed. Because of the relatively poor efficacy of interferon (IFN) monotherapy, which is ineffective in 60–70% of patients, case selection at present is determined by the likelihood of attaining a sustained response (SR; defined by normalizing serum ALT and eliminating serum HCV RNA after treatment) to therapy. According to the present study, viral load and genotype, and IL‐10 and IL‐1ra serum levels, are the most predictive of achieving SR after IFN monotherapy given in a comparatively high dose regimen for 6 months. In addition, reported studies with logistic analyses were carefully reviewed and analysed for the most effective predictive factors of case selection. The results again indicated that viral load and HCV‐genotype (serotype) were closely related to SR. Age, gender, and histological changes at treatment were also considered for case selection. These results, however, relate solely to IFN‐monotherapy. Future development of more effective strategies for treating hepatitis C could alter the exclusion criteria for IFN treatment and will negate the need for the case selection algorithm discussed here.     

No significant differences in histology and response to interferon treatment in hepatitis B carriers of genotypes C and recombinant B

Summary.  Hepatitis B virus (HBV) genotypes B and C are most prevalent in China and genotype B is found exclusively in recombination with the pre-C/C gene of genotype C. We investigated whether there is a difference in clinical relevance between the two genotypes sharing the same pre-C/C gene. Thus, we determined the genotype of HBV among consecutive HBeAg-positive patients with tailored interferon-alpha (IFN- α ) therapy, and the demographic, baseline clinical characteristics and treatment results were compared between them. The median values of alanine transaminase (ALT) were 4.5 and 5.0 times the upper limit of normal ( P  = 0.419), HBV-DNA levels were 1.4 × 10⁷ and 1.5 × 10⁷copies/mL ( P  = 0.829), mean scores of necroinflammatory histological activity 9.8 and 10.44 ( P  = 0.105) and fibrotic activity 2.64 and 2.86 ( P  = 0.227) in genotype B and C patients, respectively. The end-of-treatment response was 42.7% and 39.0% ( P  = 0.531) with mean tailored treatment months of 8.28 and 9.34 ( P  = 0.160), and the sustained response 43.4% and 37.5% ( P  = 0.31) at the end of a 12-month follow-up period in genotype B and C patients, respectively. These results remained similar when follow-up was extended to nearly 3 years. In conclusion, no significant differences in clinical characteristics and response to IFN- α between genotypes B and C were found, probably, because both types shared a common pre-C/C encoding region.     

重视女性高血压的治疗

<正> 高血压对男性和女性来说都是一种最重要的心血管危险因素,均可以导致心脑血管事件。女性在其一生中经历月经、妊娠、生育、绝经等不同的生理环节,在这些环节中女性的血压会产生何变化?如何看待女性患高血压对健康的影响?为了关注这一特殊人群高血压疾病的进程,我们有必要进一步了解女性高血压的特点和机制,提出相应的治疗对策。     

Treatment of hepatitis C with interferon and ribavirin

Hepatitis C is a worldwide problem that frequently results in end-stage liver disease and its complications. Treatment for hepatitis C virus (HCV) has been rather ineffective but several recent studies have clarified the role of interferon and ribavirin therapy. In line with therapeutic progress in HIV infection, hepatitis C is now entering the era of multidrug antiviral therapy. Ribavirin is an orally active synthetic guanosine analogue with theoretical antiviral and immunomodulatory actions. In this review we have evaluated the role of interferon and ribavirin in treatment-naive patients, relapsers and non-responders. In naive patients the combination results in improved end-of-treatment and sustained response rates, with an overall 41% sustained virological response rate in patients treated for 48 weeks. Therapeutic benefit also extends to the traditionally difficult to treat patients (genotype 1, high vital load and advanced fibrosis). The addition of ribavirin to interferon has also resulted in an increased toxicity profile, which has made therapy more difficult for both the patient and managing physician. However, the significant improvement in response rates for all patients makes combination therapy the most appropriate choice as the first-line therapy for suitable patients with chronic viral hepatitis C. Appropriate management with interferon and ribavirin includes assessing the patient's HCV genotype to determine the optimal duration of therapy, assessing therapeutic efficacy by measuring HCV-RNA at 24 weeks and monitoring for the additional ribavirin side-effects.